title: Islet autoantibodies can discriminate maturity-onset diabetes of the young (MODY) from Type 1 diabetes.
abstract: OBJECTIVE
  Maturity-onset diabetes of the young is a monogenic form of familial, young-onset diabetes. It is rare (∼1% diabetes) and may be misdiagnosed as Type 1 diabetes and inappropriately treated with insulin. Type 1 diabetes is characterized by the presence of islet autoantibodies, including glutamate decarboxylase (GAD) and islet antigen-2 (IA-2) antibodies. The prevalence of islet autoantibodies is unknown in maturity-onset diabetes of the young and may have the potential to differentiate this form of diabetes from Type 1 diabetes. The aim of this study was to determine the prevalence of GAD and IA-2 antibodies in patients with maturity-onset diabetes of the young and Type 1 diabetes.
  
  
  METHODS
  We measured plasma GAD and IA-2 antibodies in 508 patients with the most common forms of maturity-onset diabetes of the young (GCK: n = 227; HNF1A: n = 229; HNF4A: n = 52) and 98 patients with newly diagnosed Type 1 diabetes (diagnosed < 6 months). Autoantibodies were considered positive if ≥ 99th centile of 500 adult control subjects.
  
  
  RESULTS
  GAD and/or IA-2 antibodies were present in 80/98 (82%) patients with Type 1 diabetes and 5/508 (< 1%) patients with maturity-onset diabetes of the young. In the cohort with Type 1 diabetes, both GAD and IA-2 antibodies were detected in 37.8% of patients, GAD only in 24.5% and IA-2 only in 19.4%. All five patients with maturity-onset diabetes of the young with detectable antibodies had GAD antibodies and none had detectable IA-2 antibodies.
  
  
  CONCLUSIONS
  The prevalence of GAD and IA-2 antibodies in maturity-onset diabetes of the young is the same as in control subjects (< 1%). The finding of islet autoantibodies, especially IA-2 antibodies, makes the diagnosis of maturity-onset diabetes of the young very unlikely and genetic testing should only be performed if other clinical characteristics strongly suggest this form of diabetes rather than Type 1 diabetes. This supports routine islet autoantibody testing before proceeding to more expensive molecular genetic testing.
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, Exeter, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: McDonald
authors.forename: K
authors.initials: K
authors.lastname: Colclough
authors.forename: R
authors.initials: R
authors.lastname: Brown
authors.forename: B
authors.initials: B
authors.lastname: Shields
authors.forename: M
authors.initials: M
authors.lastname: Shepherd
authors.forename: P
authors.initials: P
authors.lastname: Bingley
authors.forename: A
authors.initials: A
authors.lastname: Williams
authors.forename: A T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000235:genetics / Q000276:immunology; D003937:Diagnosis, Differential; D005260:Female; D005968:Glutamate Decarboxylase / Q000097:blood* / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000097:blood* / Q000235:genetics / Q000276:immunology; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D015995:Prevalence
chemical_list: D001323:Autoantibodies; D007155:Immunologic Factors; D005968:Glutamate Decarboxylase